WNT-974

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H20N6O
Molecular Weight	396.4445
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC(=CC=N1)C2=C(C)C=C(CC(=O)NC3=CC=C(C=N3)C4=CN=CC=N4)C=N2

InChI

InChIKey=XXYGTCZJJLTAGH-UHFFFAOYSA-N

InChI=1S/C23H20N6O/c1-15-9-17(12-28-23(15)18-5-6-25-16(2)10-18)11-22(30)29-21-4-3-19(13-27-21)20-14-24-7-8-26-20/h3-10,12-14H,11H2,1-2H3,(H,27,29,30)

HIDE SMILES / InChI

Molecular Formula	C23H20N6O
Molecular Weight	396.4445
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.novartisoncology.com/our-work/research-development/key-targets/other-novel-targeted-agents | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=700477
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26658453

Novartis Oncology (previously Novartis) is developing WNT-974 (formerly LGK 974), a first-in-class selective small molecule inhibitor of O-acyltransferase. WNT-974 is under development for the treatment of cancers that are driven by the Wnt pathway in a Wnt ligand-dependent manner. Upon oral administration, WNT-974 binds to and inhibits PORCN in the endoplasmic reticulum (ER), which blocks post-translational acylation of Wnt ligands and inhibits their secretion. This prevents the activation of Wnt ligands, interferes with Wnt-mediated signaling, and inhibits cell growth in Wnt-driven tumors. Porcupine, a membrane-bound O-acyltransferase (MBOAT), is required for the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion and activity. Wnt signaling is dysregulated in a variety of cancers

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Probable protein-cysteine N-palmitoyltransferase porcupine 1 Target ID: CHEMBL1255163 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26522946	Inhibitor 8504		0.4 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Metastatic colorectal cancer 14 Sources: http://adisinsight.springer.com/drugs/800034218 https://clinicaltrials.gov/ct2/show/NCT02278133	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
72.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33941878/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		WNT-974 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
434 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33941878/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		WNT-974 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33941878/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		WNT-974 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
17.4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33941878/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		WNT-974 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	HLM 34

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681425	inconclusive [IC50 21.3174 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006720	inconclusive [IC50 5.8992 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681425	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681425	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
HLM 34	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27692509/	no

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY102756	https://www.001chemical.com/chem/search?q=DY102756
1PlusChem LLC	1P000MAY	https://www.1pchem.com/search?query=1P000MAY
AK Scientific	2140AH	https://aksci.com/item_detail.php?cat=2140AH
Ambeed	A169157	http://www.ambeed.com/search/Search.html?keyword=A169157
Angene	AGN-PC-0WAG3A	http://www.angenechemical.com/productshow/AGN-PC-0WAG3A.html
ApexBio Technology	B2307	https://www.apexbt.com/catalogsearch/result/?q=B2307
Apollo Scientific	OR302651	http://www.apolloscientific.co.uk/chemical_results.php?qstext=OR302651&product_group=%25&search_fieldname=header_search
AstaTech	CS3177	http://astatechinc.com/CPSResult.php?CRNO=CS3177
BLD Pharm	BD295733	http://www.bldpharm.com/search/Search.html?keyword=BD295733
Capot Chemical	35594	https://www.capotchem.com/search.do?q=35594
Cayman Chemical	14072	http://www.caymanchem.com/app/template/Product.vm/catalog/14072
Chem Scene	CS-2807	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2807
ChemShuttle	140515	https://www.chemshuttle.com/catalogsearch/result/?q=140515
Combi-Blocks	QM-4452	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-4452
eMolecules	49424080	https://orderbb.emolecules.com/search/#?query=49424080
eNovation Chemicals	D409774	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D409774&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A1402	http://www.excenen.com/searchresultlist.php?id=EX-A1402
Fluorochem	465541	http://www.fluorochem.co.uk/Products/Product?code=465541
KeyOrganics	MS-20504	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=MS-20504
Lab Network	LN00218237	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00218237
Lab Seeker	SC-90480	http://www.labseeker.com/search.php?keywords=SC-90480&category=0
LabSeeker	SC-90480	http://www.labseeker.com/search.php?keywords=SC-90480&category=0
Matrix Scientific	118206	http://www.matrixscientific.com/118206.html
mcule	MCULE-7022961589	https://mcule.com/MCULE-7022961589/
MedChem Express	HY-17545	https://www.medchemexpress.com/search.html?q=HY-17545&ft=&fa=&fp=
Molcore	MC102756	http://www.molcore.com/CatMC102756.html
Molnova	M10986	https://www.molnova.com/en/serch-list.html?keywords=M10986
MolPort	MolPort-029-945-290	https://www.molport.com/shop/molecule-link/MolPort-029-945-290
MuseChem	I000965	https://www.musechem.com/product/I000965.html
PI Chemicals	PI-39513	http://www.pipharm.com/catalog_products/PI-39513.html
Selleck Chemicals	S7143	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7143
ShangHai Biochempartner	BCP001048	http://www.biochempartner.com/search_BCP001048
ShangHai Biochempartner	BCP08495	http://www.biochempartner.com/search_BCP08495
SynQuest	102912	http://www.synquestlabs.com/search-result.html?q=102912
SynQuest	4H48-1-C6	http://www.synquestlabs.com/search-result.html?q=4H48-1-C6
TargetMol	T2618	https://www.targetmol.com/search?keyword=T2618

PubMed

Title	Date	PubMed
Targeting the Wnt/β-catenin pathway in primary ovarian cancer with the porcupine inhibitor WNT974.	2016-02	26658453

Patents

Sample Use Guides

In Vivo Use Guide

10 mg of WNT-974 daily by mouth

Route of Administration: Oral

In Vitro Use Guide

Ascites cells from ovarian cancer patients were treated with 1 uM WNT-974 for 7 days. Flow cytometry demonstrated fewer cells from ascites samples in the G2 phase and more in the G1 and S phases after treatment with WNT-974.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:59:20 GMT 2025` Edited by `admin` on `Mon Mar 31 21:59:20 GMT 2025`
Record UNII	U27F40013Q
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LGK-974

Preferred Name

English

WNT-974

Code

English

(2,4'-BIPYRIDINE)-5-ACETAMIDE, 2',3-DIMETHYL-N-(5-(2-PYRAZINYL)-2-PYRIDINYL)-

Systematic Name

English

LGK974

Code

English

Wnt-974 [WHO-DD]

Common Name

English

WNT974

Code

English

Code System Code Type Description

SMS_ID

100000175310